Pegylated interferon alpha-2a appears to induce a significantly better sustained virologic response than interferon alpha-2b, when combined with ribavirin in patients with chronic hepatitis C, Dr. Maria Grazia Rumi and her colleagues reported.
The two interferons differ in molecular size and structure, as well as in their pharmacokinetic and pharmacodynamic profiles. Interferon alpha-2a is administered in a fixed dose, while the dose of interferon alpha-2b is calculated according to body weight. Adverse effects differ as well. Interferon alpha-2b has been associated with lower rates of anemia, while interferon alpha-2a has been associated with lower rates of depression.
These distinctions “suggest that differences [also] may exist in safety and tolerability,” wrote Dr. Rumi of the University of Milan and her associates.
Until now, there has been insufficient evidence to support choosing one of these agents over the other. Combined with ribavirin, either is considered to be a standard of care for eradicating chronic hepatitis C virus (HCV) infection. Studies that have directly compared interferon alpha-2a and interferon alpha-2b have been “limited in sample size or scope” and have arrived at disparate conclusions, the investigators said.
The new study was a randomized, head-to-head comparison of the safety and efficacy of the two drugs in 447 patients who had not received previous treatment for chronic hepatitis C. Overall, patients assigned to receive pegylated interferon alpha-2a for 48 weeks showed a higher rate of sustained virologic response (66%) than those assigned to receive interferon alpha-2b (54%).
In the subgroup of patients with the highest levels of HCV RNA, rates of sustained virologic response were 62% with interferon alpha-2a and 48% with interferon alpha-2b. Similarly, in the subgroup of patients with cirrhosis, rates of sustained virologic response were 53% and 38%, respectively.
The researchers wrote that they were surprised that their analysis did not show cirrhosis to be a predictor of treatment failure, as it has been in previous studies of interferon. However, this study was statistically underpowered to assess the role of cirrhosis as a moderator of treatment outcome, they said.
Interferon alpha-2a also achieved higher rates of sustained virologic response (48%), compared with interferon alpha-2b (32%), in the subgroup of patients who had viral type HCV-1. Similarly, interferon alpha-2a achieved higher rates of sustained virologic response (96%) than interferon alpha-2b (82%) in the subgroup of patients who had viral type HCV-2
However, the two interferon formulations achieved similar rates of sustained virologic response in patients who had HCV-3 (65% and 69%, respectively) and in those who had HCV-4 (44% and 31%, respectively).
Rapid virologic response was the strongest predictor of a sustained response, “further supporting that early suppression of HCV is of crucial importance in the therapeutic resolution of chronic hepatitis C,” they said. Dr. Rumi reported having no conflicts of interest.